科研之友
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摘要
Introduction: Islet transplantation is a promising strategy to restore efficient insulin regulation in type 1 diabetes mellitus patients. However, shortage of islet donors, poor islet survival and toxicity of immunosuppressants often reduce the graft functional lifetime.
Methods: We previously showed that a fibroblast populated-collagen matrix (CM) significantly improved engrafted islet viability/function. However, this composite was prone to gradual biodegradation and contraction. Moreover, to avoid use of systemic immunosuppressants, we proposed the use of a local immunosuppressive enzyme, indoleamine-2,3-dioxygenase (IDO). We developed a novel bioengineered crosslinked CM (CCM) to provide optimal matrix biomimetic. Viability and insulin secretory function of islets embedded within fibroblast populated CCM (FP-CCM) was evaluated in vitro and in vivo. IDO expression was transduced in fibroblasts by a lentiviral vector carrying IDO gene and islet viability was evaluated in the presence and absence of IDO producing cells.
Results: Islet survival/function markedly improved within FP-CCM. Furthermore, our data shows that local lentiviral induction of IDO delivered by FP-CCM is nontoxic to the embedded islets.
Conclusions: This promising finding offers a new approach to improving islet transplant outcome.
- 出版日期2013-2
